Nitric Oxide in Brain Glucose Retention after Carotid Body Receptors Stimulation with Cyanide in Rats

In contrast to most other tissues, which exhibit considerable flexibility with respect to the nature of the substrates for their energy metabolism, the normal brain is restricted almost exclusively to glucose due to its distinguishing characteristics in vivo. Actual glucose utilization is 31 μmol/100 g tissue/min, in the normal, conscious human brain, indicating that glucose consumption is in excess for total oxygen consumption (Sokoloff, 1991). Although present in low concentration in brain (3.3 mmol/kg in rat), glycogen is a unique energy reserve for initiation of its metabolism. However, if glycogen concentration in the brain were the sole supply, normal energetic requirements would be maintained for less than 5 min (Sokoloff, 1991). While the brain contains insulin receptors, and insulin-responsive glucose transporters, the role of insulin in the regulation of brain glucose metabolism is controversial (Obici et al., 2002). The carotid body receptors (CBR) are sensitive to glucose (Alvarez-Buylla and Alvarez-Buylla, 1988, 1994, Pardal and Lopez Barneo, 2002) and play an important role in the insulin-induced counterregulatory response to mild hypoglycemia (Koyama et al., 2000). Local stimulation of CBR by cyanide (NaCN), or local low glucose levels in the isolated carotid sinus (CS), have been shown to promptly increase the activity in the carotid sinus nerve, that in turn trigger an enhancement in glucose retention by the brain (BGR) (Alvarez-Buylla et al., 1994). In contrast, this effect is not observed in animals with denervated carotid bodies (AlvarezBuylla and Alvarez-Buylla, 1988). The central mechanism that mediates the previously mentioned glycemic responses is unknown, but other studies from our laboratory suggest the participation of arginine-vasopressin (AVP), the endogenous ligand for the V1a vasopressin receptor, as the effector mediator in this response (Montero et al., 2003). AVP is widely synthesized in the brain, including the paraventricular, supraoptic and suprachiasmatic nuclei of the hypothalamus, and has been related to nitric oxide (NO) function in brain (Kadekaro et al., 1998). There are evidences that NO, an intercellular signaling